Serum vitamin D status is associated with prefrontal excitation-inhibition balance and functional connectivity in preschool children with autism spectrum disorder.

Purpose This study aimed to examine the associations of serum vitamin D status with medial prefrontal cortex (mPFC) neurochemistry, mPFC-centered functional connectivity, and developmental functioning in preschool children with autism spectrum disorder (ASD). Methods A total of 244 children with ASD aged 24-72 months were stratified into mild-to-moderate and severe groups according to Childhood Autism Rating Scale scores and further classified by serum 25-hydroxyvitamin D [25(OH)D] status. Proton magnetic resonance spectroscopy quantified mPFC GABA+ (γ-aminobutyric acid plus co-edited macromolecules and homocarnosine), Glx (glutamate plus glutamine), their ratios to total creatine (tCr), and the GABA+/Glx ratio, while resting-state functional MRI assessed mPFC-centered connectivity. Developmental functioning was assessed using the Griffiths Mental Development Scales-Chinese version. Correlation and serial mediation analyses were performed. Results Vitamin D status was associated with mPFC neurochemical indices and functional connectivity in both severity groups. In mild-to-moderate ASD, the deficient subgroup showed lower GABA+/tCr and GABA+/Glx, higher Glx/tCr, and reduced mPFC connectivity with the right lingual gyrus, left postcentral gyrus, and right putamen. In severe ASD, the deficient subgroup showed higher GABA+/tCr and Glx/tCr, lower GABA+/Glx, reduced mPFC-left middle occipital connectivity, and increased connectivity with the left middle temporal gyrus and left supplementary motor area. Exploratory mediation analyses identified indirect associations between 25(OH)D and personal-social development involving GABA+/tCr and mPFC-right putamen connectivity in mild-to-moderate ASD, and between 25(OH)D and hearing-language development involving Glx/tCr and mPFC-left middle temporal connectivity in severe ASD. Conclusion Serum vitamin D status was associated with mPFC excitation-inhibition-related neurochemistry, functional connectivity, and developmental functioning in preschool children with ASD. These findings may provide insight into neurobiological variation in ASD, although longitudinal studies are needed to clarify the temporal and causal relationships among vitamin D status, brain function, and developmental functioning.